2. Academic Validation
  3. Degradation of proteins by PROTACs and other strategies

Degradation of proteins by PROTACs and other strategies

  • Acta Pharm Sin B. 2020 Feb;10(2):207-238. doi: 10.1016/j.apsb.2019.08.001.
Yang Wang 1,  Xueyang Jiang 2,  Feng Feng 3 2,  Wenyuan Liu 1,  Haopeng Sun 4
Affiliations

Affiliations

  • 1 Department of Pharmaceutical Analysis, Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, Nanjing 210009, China.
  • 2 Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 211198, China.
  • 3 Jiangsu Food and Pharmaceutical Science College, Huaian 223003, China.
  • 4 Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 211198, China.
PMID: 32082969 DOI: 10.1016/j.apsb.2019.08.001
Abstract

Blocking the biological functions of scaffold proteins and aggregated proteins is a challenging goal. PROTAC proteolysis-targeting chimaera (PROTAC) technology may be the solution, considering its ability to selectively degrade target proteins. Recent progress in the PROTAC strategy include identification of the structure of the first ternary eutectic complex, extra-terminal domain-4-PROTAC-Von-Hippel-Lindau (BRD4-PROTAC-VHL), and PROTAC ARV-110 has entered clinical trials for the treatment of prostate Cancer in 2019. These discoveries strongly proved the value of the PROTAC strategy. In this perspective, we summarized recent meaningful research of PROTAC, including the types of degradation proteins, preliminary biological data in vitro and in vivo, and new E3 ubiquitin ligases. Importantly, the molecular design, optimization strategy and clinical application of candidate molecules are highlighted in detail. Future perspectives for development of advanced PROTAC in medical fields have also been discussed systematically.

Keywords

E3 ubiquitin ligase; Heterobifunctional molecule; PROTAC; Protein degradation; Target protein; Ubiquitin−proteasome system.

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